ABSTRACT Gonorrhea is a genital tract infection caused by Neisseria gonorrhoeae. It does not induce a state of specific protective immunity and can be acquired repeatedly. Despite public health measures, gonorrhea persists at an unacceptably high frequency, and there is no vaccine against it. The continued emergence of antibiotic resistance threatens to render gonorrhea untreatable. Our findings have revealed that N. gonorrhoeae subverts the immune system for its own benefit by inducing high levels of the key immunosuppressive cytokine, interleukin-10 (IL-10). Using a mouse model of vaginal gonococcal infection, our preliminary data suggests a novel strategy of immune based therapy aimed at reversing the immunosuppression induced by N. gonorrhoeae. Neutralizing antibody against IL-10 has been encapsulated in biodegradable micro-particles for local sustained release to create a proprietary product designated GneXa10. Intra-vaginal administration of GneXa10 in mice with genital gonococcal infection induces T-cell and antibody responses against N. gonorrhoeae, which accelerate clearance of the existing infection and generate resistance to re-infection with both homologous and heterologous strains. Advantages of this treatment include minimal inflammatory potential in the female reproductive tract. In this phase I application, the dose regimen of GneXa10 will be optimized. Initial mechanistic studies related to the role of B cells and duration of protection will be performed. We will also test the ability of GneXa10 to induce protection against re infection in the clinically and commercially relevant context of treatment with antibiotics. This work will provide proof-of-principle and the scientific underpinnings for GneXa10. Future SBIR phase II studies will further elucidate cross-protection and validate the expected applicability of scaled-up encapsulation methods to anti-IL-10 antibody, evaluating yield, bioactivity, batch-to-batch consistency and shelf stability. The CDC has listed drug-resistant N. gonorrhoeae as ?an immediate public health threat that requires urgent and aggressive action?, and WHO has called for ?the creation and development of new therapeutic options?. This proposal is part of our company?s response to that call to action.